A Trial of Neoadjuvant Everolimus Plus Letrozole Versus FEC in Women With ER-positive, HER2-negative Breast Cancer

NCT02742051 | Completed Phase 2 DMC

• 1 other identifier: 50102016015
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This open, randomized pilot feasibility trial is to evaluate the feasibility and effect of neoadjuvant everolimus plus letrozole versus neoadjuvant fluorouracil, epirubicin plus cyclophosphamide (FEC) in treating postmenopausal women with ER-positive, HER2-negative breast cancer. Forty postmenopausal stage M0, ER-positive, HER2-negative invasive breast cancer women who had a primary tumor \> 2cm by imaging or an axillary lymph node \> 2cm by imaging were randomly (1:1) enrolled to receive neoadjuvant everolimus plus letrozole for 18 weeks or neoadjuvant FEC for 6 cycles before surgery. The primary objective is to determine the feasibility of neoadjuvant everolimus plus letrozole in postmenopausal patients with ER-positive, HER2-negative breast cancer. Secondary aims are to compare the ultrasound response rate, pathological complete response (pCR) rate, breast-conserving surgery rate, toxicities, and changes in the percentages or counts of peripheral blood CD4+ T cells, CD8+ T cells, tumor-specific CTLs, T helper cells (Th), regulatory T cells (Treg), and NK cells and changes in tumor Ki67 index (pre- versus post- neoadjuvant therapy).

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Feasibility of the trial

  during on-neoadjuvant therapy period (defined as the period from the first dose of study medication up to 30 days of the last dose)

Secondary Outcomes (11)

• Ultrasound response rate

  at definitive surgery (18-20 weeks after the first dose of study medication)

• Pathological complete response (pCR) rate

  at definitive surgery (18-20 weeks after the first dose of study medication)

• Breast-conserving surgery rate

  at definitive surgery (18-20 weeks after the first dose of study medication)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  during on-neoadjuvant therapy period (defined as the period from the first dose of study medication up to 30 days of the last dose)

• Peripheral blood CD8+ T cell percentage change in relation to neoadjuvant therapy

  at definitive surgery (18-20 weeks after the first dose of study medication)

Study Arms (2)

Everolimus+Letrozole

EXPERIMENTAL

everolimus 10mg/d,po + letrozole 2.5mg/d,po \* 18 weeks

Drug: Everolimus; Drug: Letrozole

Fluorouracil+epirubicin+cyclophosphamide

ACTIVE COMPARATOR

Fluorouracil 600mg/m2,iv,d1 + epirubicin 90mg/m2,iv,d1 + cyclophosphamide 600mg/m2,iv,d1 \* 6 cycles (every 21 days per cycle)

Drug: Fluorouracil; Drug: Epirubicin; Drug: Cyclophosphamide

Interventions

Everolimus DRUG

Neoadjuvant endocrine therapy

Also known as: RAD001

Everolimus+Letrozole

Letrozole DRUG

Neoadjuvant endocrine therapy

Also known as: Femara

Everolimus+Letrozole

Fluorouracil DRUG

Neoadjuvant chemotherapy

Also known as: 5-Fu

Fluorouracil+epirubicin+cyclophosphamide

Epirubicin DRUG

Neoadjuvant chemotherapy

Also known as: EPB

Fluorouracil+epirubicin+cyclophosphamide

Cyclophosphamide DRUG

Neoadjuvant chemotherapy

Also known as: CTX

Fluorouracil+epirubicin+cyclophosphamide

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patients signed the written informed consent
• The patients present with non-metastatic unilateral invasive ER-positive, HER2-negative breast cancer with a primary breast tumor \> 2cm by imaging or an axillary lymph node \> 2cm by imaging.
• Postmenopausal women with age less than 70 years old.
• The patients have no history of hormone therapy, chemotherapy, breast cancer surgery and radiotherapy.
• The patients have normal cardiac functions by echocardiography.
• The patients' ECOG scores are ≤2.
• The patients can swallow pills.
• The results of patients' blood tests are as follows:
• Hb≥90g/L;
• WBC≥4E+9/L;
• Plt≥100E+9/L;
• Neutrophils≥1.5E+9/L;
• ALT and AST ≤ triple of normal upper limit;
• TBIL ≤ 1.5 times of normal upper limit;
• Creatinine ≤ 1.5 times of normal upper limit.

You may not qualify if:

• The patients have other cancers at the same time or have the history of other cancers except controlled skin basal cell carcinoma or skin squamous cell carcinoma or carcinoma in situ of cervix uterus;
• The patients have active infections that were not suitable for chemotherapy;
• The patients have severe non-cancerous diseases.
• The patients have bilateral breast cancers or multifocal breast cancers or inflammatory breast cancers.
• The patients have a history of previous treatment with mTOR inhibitors.
• The patients are undergoing current administration of anti-cancer therapies, or are attending other clinical trials.
• The patients are in some special conditions that they cannot understand the written informed consent, such as they are demented or hawkish.
• The patients have allergic history or contraindication of any of the interventional drugs.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun-Yat-Sen Memorial Hospital of Sun-Yat-Sen University

Guangzhou, Guangdong, 510120, China

Location

Related Publications (2)

• Wu W, Chen J, Deng H, Jin L, He Z, Rao N, Nie Y, Yao Y, Yang Y, Su F, Liu J. Neoadjuvant everolimus plus letrozole versus fluorouracil, epirubicin and cyclophosphamide for ER-positive, HER2-negative breast cancer: a randomized pilot trial. BMC Cancer. 2021 Jul 27;21(1):862. doi: 10.1186/s12885-021-08612-y.

  PMID: 34315439 DERIVED

• Wu W, Deng H, Rao N, You N, Yang Y, Cao M, Liu J. Neoadjuvant everolimus plus letrozole versus fluorouracil, epirubicin and cyclophosphamide for ER-positive, HER2-negative breast cancer: study protocol for a randomized pilot trial. Trials. 2017 Oct 25;18(1):497. doi: 10.1186/s13063-017-2228-5.

  PMID: 29070044 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus; Letrozole; Fluorouracil; Epirubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Jieqiong Liu, M.D.,Ph.D.

  Breast Tumor Center, Sun Yat-sen Memorial Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Surgeon of Breast Tumor Center

Study Record Dates

• First Submitted: April 7, 2016
• First Posted: April 18, 2016
• Study Start: June 1, 2016
• Primary Completion: March 14, 2020
• Study Completion: March 14, 2020
• Last Updated: September 23, 2021

Record last verified: 2021-09

Locations

CN (1)